7. Project Summary The design of the study remains the same as the ongoing project, however, two major sub-objectives are planned. The temporal circulation of influenza in India suggests the current fall immunization schedule may not be optimal. The proposed study will provide data on vaccine timing that will have broad implications in tropical settings. Specific Aim 1. Describe influenza vaccine direct and indirect efficacy. Accomplished by determining the efficacy of vaccination of children in decreasing influenza in children and their family members in 3 rural villages in India in a prospective, controlled, household randomized, observer blinded study. Two phases are proposed: Phase 1: Continue determination of efficacy against influenza with multiple vaccine years. The efficacy of influenza vaccine depends in part on antigenic match with circulating viruses. Vaccination in 2009 had a poor match due to the pandemic, 2010 vaccination had an improved match and if vaccination in fall 2011 (as requested here) provides a match, with surveillance until May 2012 a cumulative protective effect can be assessed for 2-3 years after fall administration. At this time, phase 2 begins. Phase 2: To determine the efficacy of vaccine administered prior to the monsoon influenza peak in Northern India. The largest peak of influenza is observed in summer in the Delhi region, with minor peaks in winter. We hypothesize that influenza vaccination in late spring prior to the influenza peak in summer in Northern India will confer significantly better protection during the period of highest influenza activity, compared to the current vaccination regimen in the fall of the year. We propose to test a change of timing, immunizing in May 2012 and 2013, with follow-up until May 2014. This will measure direct and indirect protection after both fall and spring immunization and extend the years of data, without compromising the overall objectives of the study. This regimen may lead policy makers to adjust recommendations for the timing of influenza vaccination. Specific Aim 2. Define influenza clinical disease and outcomes. The clinical presentations of influenza, including co-morbid conditions and influenza-related complications are recorded from active weekly surveillance in the study villages comprising >16,000 persons. Furthermore testing for other non-influenza respiratory viruses will estimate their contribution to disease in this population. In summary, the proposed studies will determine whether immunization of young children with influenza virus vaccine protects not only the immunized children but also the other children and adults who are around them, and will identify the appropriate timing of vaccine administration in India and other regions with similar influenza seasonality.